Serum Pregnancy-associated Plasma protein-A Levels Research Articles

Correlation between PAPP-A serum levels in the first trimester of pregnancy with the occurrence of gestational diabetes, a multicenter cohort study

ObjectiveThis study aimed to investigate the association between first-trimester Pregnancy-associated plasma protein A (PAPP-A) levels and subsequent gestational diabetes mellitus (GDM) development.MethodThe study was conducted on 5854 pregnant women who attended routine prenatal care. Maternal biomarkers, including PAPP-A and free beta hCG, were measured for all women in a referral laboratory and converted to MoM values. Pregnant women were divided into two groups, based on the serum concentration of PAPP-A, (PAPP-A > 0.4 (normal) and PAPP-A < 0.4 (low)). Data on the screening test for GDM and pregnancy outcomes were collected and analyzed with appropriate tests.ResultOf the 5854 pregnant women, 889 (15.19%) developed GDM. The maternal PAPP-A MoM concentrations were significantly lower in GDM cases compared to controls. Indeed, gestational age at delivery and birth weight were significantly lower (p < 0.001) in PAPP-A MoM < 0.4, and the rate of intrauterine growth restriction (IUGR) was significantly higher (p < 0.001). ROC analysis revealed that the sensitivity and specificity of MoM concentration for predicting GDM were 53.3% and 51.9%, respectively.ConclusionLower maternal PAPP-A in early pregnancy can lead to glucose intolerance and increase the risk of subsequent GDM development. In addition, decreased serum concentration of PAPP-A is significantly correlated to lower birth weight and IUGR.

Meta-analysis for the relationship between circulating pregnancy-associated plasma protein A and placenta accreta spectrum.

Changes in circulating pregnancy-associated plasma protein A (PAPP-A) have been observed in women with a placenta accreta spectrum (PAS). However, no consensus has been reached according to the previous studies. Our study investigated the relationship between circulating PAPP-A and PAS risk through a systematic review and meta-analysis. Studies comparing the circulating level of PAPP-A between pregnant women with and without PAS were obtained by searching the Medline, Cochrane Library, Embase, CNKI, and Wanfang databases from the inception of the databases until February 12, 2023. Heterogeneity was considered in the pooling of results via a random-effects model. Eight observational studies were obtained for the meta-analysis, which included 243 pregnant women with PAS and 1599 pregnant women without PAS. For all these women, the first-trimester circulating level of PAPP-A was measured by immunoassay and reported as multiples of the median (MoM) values. The pooled results showed that compared to those who did not develop PAS, women with PAS had significantly higher first-trimester serum level PAPP-A (mean difference: 0.43 MoM, 95% confidence interval [CI]: 0.30 to 0.56, P < .001; I2 = 32%). Furthermore, a high first-trimester serum PAPP-A level was related to a high PAS risk (odds ratio: 2.89, 95% CI: 2.13 to 3.92, P < .001; I2 = 0%). Sensitivity analysis which excluded one study at a time, also obtained similar results (p all < 0.05). Pregnant women with a high serum PAPP-A level in the first trimester may be at an increased risk for PAS.

Pregnancy-Associated Plasma Protein-A: Its Significance as a Single Biomarker for Adverse Obstetric Outcomes

OBJECTIVES: Low levels of pregnancy-associated plasma protein-A in pregnant women linked to unhealthy placentation and a spectrum of maternal and fetal complications. Its assessment as a single biomarker has the potential to identify high-risk pregnancies. This prospective observational study was conducted to find a correlation between low pregnancy-associated plasma protein-A levels in the first trimester of pregnancy with various obstetric outcomes to establish if it can be used as a single biomarker for counseling couples. STUDY DESIGN: The study was conducted at Base Hospital, Delhi Cantt. Maternal serum pregnancy-associated plasma protein-A levels were assessed at 11 to 13+6 weeks of gestation, converted in multiples of the median and patients were followed till delivery. Maternal outcomes were recorded in terms of abortions, development of gestational hypertension, gestational diabetes, preeclampsia, placental abruption, fetal growth restriction, fetal demise, neonatal intensive care unit admission, etc., and analyzed to find an association with levels first trimester of pregnancy-associated plasma protein-A. RESULTS: Low pregnancy-associated plasma protein-A levels showed a statistically significant association with gestational hypertension, preeclampsia, abortion, fetal demise, and also for adverse neonatal outcomes like APGAR &lt;5 at 1 min, fetal growth restriction, neonatal intensive care unit admission, and perinatal deaths. No significant association was observed for preterm delivery, gestational diabetes, and placental abruption. CONCLUSION: Serum pregnancy-associated plasma protein-A levels in the first trimester of pregnancy have the potential of being utilized as a validated marker for adverse pregnancy outcomes. Early identification of such pregnancies can help in optimizing feto-maternal outcomes through closer surveillance, timely intervention, and referral to tertiary care centers. Further research would help the fraternity in developing a prediction model.

Investigation of cardiovascular risk parameters in adolescents with metabolic syndrome.

Metabolic syndrome leading to type 2 diabetes mellitus and cardiovascular diseases is a chronic multifactorial syndrome, associated with low-grade inflammation status. In our study, we aimed at assessing the serum levels of follistatin (FST), pregnancy-associated plasma protein-A (PAPP-A), and platelet/endothelial cell adhesion molecule-1 (PECAM-1) in adolescent patients with metabolic syndrome. This study was performed in 43 (19 males, 24 females) metabolic syndrome adolescents and 37 lean controls matched for age and sex. The serum levels of FST, PECAM-1, and PAPP-A were measured by using ELISA method. Serum FST and PAPP-A levels in metabolic syndrome were significantly higher than those of controls (p < 0.005 and p < 0.05). However, there was no difference in serum PECAM-1 levels between metabolic syndrome and control groups (p = 0.927). There was a significant positive correlation between serum FST and triglyceride (r = 0.252; p < 0.05), and PAPP-A and weight, (r = 0.252; p < 0.05) in metabolic syndrome groups. Follistatin was determined statistically significant in both univariate (p = 0,008) and multivariate (p = 0,011) logistic regression analysis. Our findings indicated a significant relationship between FST and PAPP-A levels and metabolic syndrome. These findings offer the possibility of using these markers in diagnosis of metabolic syndrome in adolescents as the prevention of the future complications.

Study on the Relationship and Predictive Value of First-Trimester Pregnancy-Associated Plasma Protein-A, Maternal Factors, and Biochemical Parameters in Gestational Diabetes Mellitus: A Large Case-Control Study in Southern China Mothers.

To investigate the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical parameters with gestational diabetes mellitus (GDM) in southern China mothers. This study recruited 4872 pregnant women. PAPP-A, the free beta subunit of human chorionic gonadotropin (free β-HCG), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and high- and low-density lipoproteins (HDL, LDL) were measured at 11-13+ weeks of gestation. GDM was diagnosed based on a 75 g oral glucose tolerance test at 24-28 weeks of gestation. We performed stepwise logistic regression analysis to determine the odds ratio (OR) and the 95% confidence interval (CI) of GDM. We used Receiver Operating Characteristic (ROC) curves with the area under the curve (AUC) to evaluate the predictive value of PAPP-A, maternal factors, and biochemical markers. The significance of the differences between the AUC values was assessed using the DeLong test. GDM was diagnosed in 750 (15.39%) women. Independent factors for GDM were age, pre-gestational BMI, GWG before a diagnosis of GDM, previous history of GDM, family history of diabetes, FPG, TG, LDL, PAPP-A, and TC. The AUC of PAPP-A was 0.56 (95% CI 0.53-0.58). The AUC of a model based on combined maternal factors, biochemical markers, and PAPP-A was 0.70 (95% CI 0.68-0.72). Differences in AUC values between PAPP-A alone and the model based on combined maternal factors, biochemical markers, and PAPP-A were statistically significant (Z= 9.983, P<0.001). A Low serum PAPP-A level in the first trimester is an independent risk factor for developing GDM later in pregnancy. However, it is not a good independent predictor although the predictive value of a low serum PAPP-A level increases when combined with maternal factors and biochemical markers.

Serum biochemical parameters in pregnant women with and without fetal chromosomal abnornalities

Aim. To analyse the levels of serum beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in pregnant women without fetal chromosomal abnormalities and with fetal trisomy 21 (Down syndrome) or 18 (Edwards syndrome).Materials and Methods. We performed a retrospective analysis of serum biochemical parameters of 1214 women who had previously undergone karyotyping as a part of prenatal or postnatal screening. Patients were stratified into those with a normal fetal karyotype, those carrying a fetus with trisomy 21, and those carrying a fetus with trisomy 18. Levels of serum β-hCG and PAPP-A were estimated using the AutoDELFIA automatic immunoassay system.Results. In most of the women carrying a fetus with trisomy 21, serum β-hCG has been increased as compared to the reference range. In contrast, women carrying a fetus with trisomy 18 generally had reduced serum β-hCG. In both cases, the level of serum PAPP-A has been decreased in comparison with a reference range. The proportion of women with a 2-fold reduced serum PAPP-A was 52.4% and 88.6% if carrying fetuses with trisomy 21 and trisomy 18, respectively.Conclusion. Serum b -hCG has been increased as compared to the reference range. In contrast, women carrying a fetus with trisomy 18 generally had reduced serum β-hCG. In both cases, the level of serum PAPP-A has been decreased in comparison with a reference range. The proportion of women with a 2-fold reduced serum PAPP-A was 52.4% and 88.6% if carrying fetuses with trisomy 21 and trisomy 18, respectively.Conclusion. Serum b-hCG and PAPP-A are sensitive markers of fetal trisomy 21 and trisomy 18 in pregnant women.

Correlations between maternal hepatitis B virus carrier status and Down’s syndrome prenatal screening indicators and their effects on the screening results

The aim of this study was to determine the correlation between maternal hepatitis B virus (HBV) carrier status and pregnancy-associated serum screening indicators, as well as their implications on the prenatal screening results of Down’s syndrome (DS). This retrospective cohort study included two groups, namely the healthy gravidas group (n = 19804) and the maternal HBV carrier group (n = 792). Serum pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), and free beta subunit of human chorionic gonadotropin (free β-hCG) levels, as well as the foetal nuchal translucency (NT) thickness, were measured. Multivariatebinary logistic regression analysis was used to evaluate the association between the HBV carrier status and prenatal screening biomarkers. The PAPP-A multiple of the medium (MoM) and free β-hCG MoM in the first trimester were significantly higher in the HBV carrier group than in the control group (both P < .05). Multivariate binary logistic regression analysis showed that HBV carrier status was identified as a risk factor for PAPP-A and the intrahepatic cholestasis of pregnancy (ICP), with adjusted odds ratios (aOR) of 1.363 (1.216–1.527) and 3.255 (2.356–4.499), respectively. Pregnant women with HBV carrier status had higher influence on serum PAPP-A level and ICP, and the risk calculation algorithm for DS in HBV carriers should be corrected in the first trimester of pregnancy. IMPACT STATEMENT What is already known on this subject? The maternal serum levels of pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), and free beta subunit of human chorionic gonadotropin (free β-hCG), as well as the foetal nuchal translucency (NT) thickness, have been collectively used in the prenatal screening of Down’s syndrome (DS), Edward’s syndrome (ES), and open neural tube defects (ONTD). However, many factors, including the maternal age; maternal weight; gestational age; race; history of smoking and so on can affect those serum biomarker levels. Our aim is to know whether there is a difference for HBV status to pregnancy-associated serum screening indicators hoes. What the results of this study add? The PAPP-A multiple of the medium (MoM) and free β-hCG MoM in the first trimester were significantly higher in the HBV carrier group than in the control group (both p < .05). Multivariate binary logistic regression analysis showed that the PAPP-A and intrahepatic cholestasis of pregnancy (ICP) were risk factors for HBV carriers, with aORs of 1.363 (1.216–1.527) and 3.255 (2.356–4.499), respectively. What the implications are of these findings for clinical practice and/or further research? The PAPP-A MoM in maternal HBV carriers was significantly higher than that in healthy gravidas, and the risk calculation algorithm for DS in maternal HBV carriers should be corrected in the first trimester of pregnancy.

Value of PAPP-A combined with BMI in predicting the prognosis of gestational diabetes mellitus: an observational study

The aim of this study was to investigate the potential of pregnancy-associated plasma protein A (PAPP-A) and clinical data in predicting gestational diabetes mellitus (GDM). Clinical data of 318 pregnant women with GDM and 200 healthy pregnant women were retrospectively analysed. The age, BMI and caesarean section in GDM were significantly higher than in normal group. Serum and placental levels of PAPP-A were significantly lower in GDM than in normal group. Pearson’s correlation analysis showed that serum levels of PAPP-A were negatively correlated with BMI and blood glucose level. Binary logistic regression analysis displayed that PAPP-A were the potential factors influencing GDM. The area under the ROC curve (AUC) for PAPP-A combined with BMI in predicting GDM was 0.941, significantly higher than that of the single one. The potential of PAPP-A in the first trimester is limited in predicting GDM. PAPP-A combined with BMI is highly conductive for predicting GDM. Impact statement What is already known on this subject? GDM not only increases the risk of perinatal morbidity, but also results in an increased risk of long-term sequelae for both mother and child including diabetes, cardiovascular disease obesity. Previous data indicate that besides glycemic control in the second trimester, interventions initiated early in pregnancy can reduce the rate of GDM in pregnant women. The expression of PAPP-A in serum of GDM pregnant women was decreased in the first trimester. Whereas, whether PAPP-A can be as an early predictor of GDM is not clear. What do the results of this study add? The present study shows that PAPP-A MoM was less than 0.6757 in the first trimester of pregnancy is more prone to GDM. The potential of PAPP-A in the first trimester is limited in predicting GDM. PAPP-A combined with BMI is highly conductive for predicting GDM. What are the implications of these findings for clinical practice and/or further research? Early GDM prediction is crucial for prevention and management of GDM, to cope with the rising prevalence of GDM and reduce later life chronic disease of both mother and child. Based on the level of PAPP-A MoM and BMI, interventions such as lifestyle changes initiated early in pregnancy shouldbeenabledin pregnant women.

The Correlation Between Serum Pregnancy Associated Plasma Protein A (PAPP-A) with the Endometrial Thickness and Resistance Index and their Effect on Pregnancy Outcome for Infertile Women Undergo ICSI Cycle

Pregnancy-associated plasma protein-A (PAPP-A) is approved to be not pregnancy specific; it could be localized in nonpregnant women endometrium. Thus, it was of interest to see if PAPP-A can be capable of preparing the uterine endometrium for implantation. However, the relationship between serum PAPP-A and endometrium receptivity remains unclear. To evaluate if there is any correlation between the level of serum pregnancy associated plasma protein-A (PAPP-A) with the endometrial thickness and resistance index and evaluate their effects of pregnancy outcome for patient's candidate for intracytoplasmic sperm injection (ICSI). This is a prospective study that was submitted at the infertility center of High Institute for Infertility Diagnosis and Assisted Reproductive Technologies, Al-Nahrain University, Baghdad, Iraq, from November 2020 till March 2021. Forty-five infertile females participated in the study, younger than 40 years old submitted to antagonist protocol. For assessment of endometrium receptivity, transvaginal ultrasound was done at days of oocyte pickup and embryo transfer to measure the endometrial thickness and the resistance index. Serum PAPP-A was measured at the day of oocyte pickup and at day of embryo transfer. Two weeks later, a pregnancy test was done for all patients and according to the result the patients divided into two groups pregnant (n=20) and non-pregnant (n=25). There was insignificant positive correlation between serum PAPP-A level with endometrial thickness (ET) and insignificant negative correlation with (RI) at day of oocyte pick up and day embryo transfer. High serum Pregnancy associated plasma protein-A (PAPP-A) may be associated with an increase in endometrial thickness and low level of resistance index that both may promote the possibility of implantation.

Prediction of spontaneous preterm birth and preterm prelabor rupture of membranes using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks.

To determine whether first-trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB), and to develop prediction models using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risk for sPTB. This was a retrospective secondary analysis of data derived from a prospective cohort study on first-trimester screening for pre-eclampsia in singleton pregnancies attending for routine Down syndrome screening at 11 + 0 to 13 + 6 weeks' gestation at a tertiary obstetric unit between December 2016 and September 2019. A split-sample internal validation method was used to explore and develop prediction models for all sPTB at < 37 weeks and for PTB at < 37 weeks after preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG). Screening performance was assessed using receiver-operating-characteristics (ROC)-curve analysis, with calculation of the areas under the ROC curves (AUCs). A total of 9298 singleton pregnancies were included in this study. sPTB at < 37 weeks occurred in 362 (3.89%) cases, including 231 (2.48%) cases of PPROM. sPTB at < 34 weeks occurred in 87 (0.94%) cases, including 39 (0.42%) cases of PPROM. Identified maternal risk factors for sPTB at < 37 weeks included chronic hypertension, conception using in-vitro fertilization and history of PTB. Maternal risk factors for PPROM at < 37 weeks included conception using in-vitro fertilization and history of PTB. Median PlGF multiples of the median (MoM) and PAPP-A MoM were significantly reduced in women with sPTB at < 37 weeks, as well as in those who had PPROM, compared to those who delivered at term. Screening by a combination of maternal risk factors, PAPP-A and PlGF achieved better performance in predicting sPTB at < 37 weeks (AUC, 0.630 vs 0.555; detection rate (DR), 24.8% vs 16.6% at a false-positive rate (FPR) of 10%; P ≤ 0.0001) and PPROM at < 37 weeks (AUC, 0.643 vs 0.558; DR, 28.1% vs 17.0% at a FPR of 10%; P ≤ 0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUCs of 0.628 and 0.650, respectively. We demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM at < 37 weeks. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model that includes maternal risk factors, PAPP-A and PlGF before clinical application. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

A retrospective cohort study on the effects of Down’s screening markers and maternal characteristics on pregnancy outcomes in preeclampsia

ABSTRACT Background To investigate the effects of down’s screening markers and maternal characteristics on preeclampsia (PE) pregnancy outcome during early and middle pregnancy. Methods A retrospective study of a cohort of 246 PE and 18,709 No-PE pregnant women who participated in Down’s screening during early and middle pregnancy was performed. Clinical data of pregnancy-related were collected. Multivariate binary logistic regression was used to analyze the adjusted odds ratio (aOR) and 95% confidence interval (CI) of Down’s screening markers, maternal characteristics, pregnancy outcome, and other related variables, and to evaluate the influencing factors of each indicator on PE. P < .05 was considered to be statistically significant. Results Compared with the non-PE group, the concentration and median multiple (MoM) of pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) in PE group were both lower (P < .001). Multivariate binary logistic regression analysis showed that low birth weight, hydronephrosis, premature delivery, fetal growth retardation, cesarean section, live birth, hyperlipemia, infection, decreased free β-hCG and first trimester maternal weight were risk factors for PE (aOR were: 7.552, 6.684, 4.154, 3.762, 3.612, 2.454, 1.757, 1.562, 1.270, and 1.077, respectively), while uterine scar, premature rupture of membranes and elevated PAPP-A were protective factors of PE (aOR were: 0.222, 0.328 and 0.612, respectively). Conclusion Decreased maternal serum PAPP-A level, increased free β-hCG, hyperlipemia, premature delivery, cesarean section, live birth, hydronephrosis, fetal growth retardation, low birth weight, and infection are risk factors for PE, while uterine scar and premature rupture of membrane are protective factors for PE.

P-769 Endometrial thickness is not associated with birthweight as well as serum levels of pregnancy-associated plasma protein-A: a retrospective analysis of 560 newborns following frozen cycles

Abstract Study question Does endometrial thickness (EMT) affect birthweight and maternal serum evels of pregnancy-associated plasma protein-A (PAPP-A) in singleton pregnancies following frozen-thawed blastocyst transfer (FET)? Summary answer EMT does not significantly affect birthweight and maternal serum evels of PAPP-A in singleton pregnancies following FET. What is known already Several studies have shown an association between EMT and low birth weight in pregnancies resulting from fresh embryo transfers. Supraphyiological levels of steroid hormone during ovarian stimulation may be responsible for poor fetal growth. Few studies have investigated the relationship between EMT and fetal growth potential in frozen-thawed embryo transfers. Study design, size, duration This retrospective study included women who underwent first-trimester combined screening for aneuploidy after frozen-thawed blastocyst transfer and subsequently delivered a singleton live birth after 24 weeks of gestations between January 2016 and July 2020 in a private IVF center. Participants/materials, setting, methods A total of 560 women met the inclusion criteria and were stratified into three groups based on the EMT percentiles: &amp;lt;7.7 mm (&amp;lt;10th percentile), 7.7–12 mm (10-90th percentile), and &amp;gt;12 mm (&amp;gt;90th percentile). The primary outcome measures were mean birth weight and mean PAPP-A level. A multivariable linear regression analysis was carried out to identify the association between birth weight and EMT after adjusting for variables found at &amp;lt; 0.1 level in the univariate analysis. Main results and the role of chance The mean birth weight was 3127 ± 783 g in those with EMT &amp;lt;7.7 mm 3225 ± 644 g in those with EMT 7.7-12 mm, and 3256 ± 599 g in those with EMT &amp;gt;12 mm (p = 0.577). The mean PAPP-A levels and PAPP-A&amp;lt;0.5 rates were similar in the groups, as well. In multivariate analysis, the number of previous ART attempts and maternal serum levvels of PAPP-A were found to be significant predictors of birth weight (p = 0.001 and p = 0.013, respectively). EMT was not a predictor of birth weight in both univariate and multivariate analyses. The multivariate logistic regression analysis indicated that the number of previous ART attempts was an independent factor for low birth weight (OR:1.39, 95%CI:1.09-1.76, p = 0.006). Limitations, reasons for caution The study has inheret limitations due to its retrospective nature. Further studies are needed to investigate the relationship between EMT and birth weight along with maternal serum levels of PAPP-A. Wider implications of the findings Our study provided a new angle of view for evaluating the association between EMT and neonatal birth weight by analyzing this association along with maternal serum levels of PAPP-A as a marker for placental function, suggesting that EMT is not an independent factor for neonatal birth weight. Trial registration number NA

Relationship between extreme values of first trimester maternal pregnancy associated plasma Protein-A, free-β-human chorionic gonadotropin, nuchal translucency and adverse pregnancy outcomes

ObjectiveThe aim of our study was to investigate the relationship between extreme values of first trimester screening markers and adverse obstetric outcomes. Materials and methodsOur study was conducted by examining the prenatal and postnatal perinatal records of 786 singleton gestations between the ages of 18–40, who applied to Prof. Dr. Cemil Taşçıoğlu City Hospital outpatient clinics for first-trimester screening for aneuploidy, between January 1, 2017 and December 31, 2019. ResultsThe presence of small for gestational age (SGA) was found to be statistically significant for the <5 percentile (<0.37) pregnancy-associated plasma protein A (PAPP-A) group (p = 0.016). For <5 percentile β-hCG group, the presence of gestational diabetes mellitus (GDM), premature rupture of membrane (PROM) and preterm premature rupture of membrane (PPROM) was determined as a statistically significant risk (p = 0.015, p = 0.005, p = 0.02 respectively) In the univariate test, fetal death rate was found to be high for ≥90 percentile at nuchal translucency (NT), but the presence of fetal death was found to be statistically insignificant in logistic regression analysis. (p: 0.057). ConclusionFirst trimester screening test can be used in predicting pregnancy complications. In this study we found that serum levels of PAPP-A are associated with developing SGA, while GDM, PROM and PPROM are more common in low serum free β-hCG.

Prediction of Preeclampsia Using First-Trimester Uterine Artery Doppler and Pregnancy-Associated Plasma Protein-A (PAPP-A): A Prospective Study in Chhattisgarh, India

IntroductionPreeclampsia is a major contributor of maternal and perinatal morbidity and mortality. Uterine artery waveform and biomarkers like pregnancy-associated plasma protein-A (PAPP-A) may reflect the pathophysiology of preeclampsia. Thus, we aim to find out whether abnormal uterine artery pulsatility index (PI) and low serum PAPP-A in the first trimester can predict preeclampsia.MethodologyAntenatal women at 11-13+6 weeks of gestation visiting All India Institute Of Medical Science (AIIMS) in Raipur were enrolled after informed consent. Uterine artery Doppler was done with the early anomaly scan at 11-13+6 weeks. Serum levels of PAPP-A were analyzed. The women were followed up at intervals up to delivery. Incidence of preeclampsia and gestational hypertension was noted.ResultsThe incidence of preeclampsia was 12.7%, and that of gestational hypertension was 4.9%. The mean uterine artery PI among those who developed hypertension in pregnancy was 2.007, which was significantly higher than the unaffected group (p=0.01). The first-trimester uterine artery PI as a screening tool showed a sensitivity of 68%, specificity of 52.99%, and detection rate (DR) of 55.63%.The mean PAPP-A MoM of the affected group was 0.67 which was significantly higher than the unaffected group (p<0.001). The first trimester PAPP-A as a screening tool showed a sensitivity of 28%, specificity of 90.6%, and DR of 79.58%.ConclusionBoth the tests were concluded to be good predictors of hypertension in pregnancy. Identification of high-risk factors, screening, and surveillance are of utmost importance in order to predict preeclampsia and initiation of preventive therapy.

Increase in Ischemia-Modified Albumin and Pregnancy-Associated Plasma Protein-A in COVID-19 Patients.

This study was undertaken due to the urgent need to explore reliable biomarkers for early SARS-CoV-2 infection. We performed a retrospective study analyzing the serum levels of the cardiovascular biomarkers IL-6, TNF-α, N-terminal pro-B natriuretic peptide, cardiac troponin T (cTnT), ischemia-modified albumin (IMA) and pregnancy-associated plasma protein-A (PAPP-A) in 84 patients with COVID-19.Patients were divided into three groups according to their RT-qPCR and IgG values: acute infection (n = 35), early infection (n = 25) or control subjects (n = 24). Levels of biomarkers were analyzed in patient serum samples using commercially available ELISA kits. Results showed a significant increase in IMA and PAPP-A levels in the early infected patients. Moreover, multivariate analysis and receiver operating characteristic (ROC) curve showed that IMA and PAPP-A had excellent discrimination value for the early stage of COVID-19. For IMA, the area under the ROC curve (AUC) had a value of 0.94 (95% confidence interval (CI): 0.881–0.999). Likewise, the serum level of PAPP-A was significantly higher in patients with early infection than in the control subjects (AUC = 0.801 (95% CI: 0.673–0.929)). The combined use of IMA and PAPP-A enhanced the sensitivity for total SARS-CoV-2-infected patients to 93%. These results suggest that the increased levels of PAPP-A and IMA shed light on underlying mechanisms of COVID-19 physiopathology and might be used as efficient biomarkers with high sensitivity and specificity for the early stage of COVID-19. Importantly, when monitoring pregnancy and cardiovascular diseases using PAPP-A or IMA levels, a SARS-CoV-2 infection should be discarded for proper interpretation of the results.

The Relationship Between First-Trimester Aneuploidy Markers and Birth Weight

OBJECTIVE: We aimed to determine the relationship between the first-trimester aneuploidy screeningma and the predicted weight at birth: Small for gestational age and large for gestational age. STUDY DESIGN: 594 low-risk pregnant women with a singleton pregnancy, who underwent first-trimester aneuploidy screening by measuring nuchal translucency, maternal serum free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein-A were included in the study. Those weighing above the 3rd percentile and below the 10th percentile were defined as small for gestational age, and those over the 90th percentile were defined as large for gestational age. RESULTS: A total of 594 pregnant women were enrolled. The mean maternal age of the studied group was 28.8±5.5 years. Low maternal serum pregnancy-associated plasma protein-A levels and decreased nuchal translucency measurements were associated with the small for gestational age newborn (p&lt;0.001 and p=0.001, respectively). There is a significant correlation with large for gestational age for newborns only with an increase in maternal serum pregnancy-associated plasma protein-A levels (p=0.001). beta-human chorionic gonadotropin levels were not associated with the birth weight (p=0.735). CONCLUSION: Maternal serum pregnancy-associated plasma protein-A levels, one of the markers in first-trimester aneuploidy screening, can be used in the prediction of small for gestational age and large for gestational age However, due to its low correlation, it is not a suitable screening test for clinical practice.

Potential role of biochemical placentation markers - pregnancy associated plasma protein-A and human chorionic gonadotropin for early gestational diabetes screening - a pilot study.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. The universal screening for GDM is usually performed between 24-28 weeks' gestation. This often delays the diagnosis and could increase the risk of adverse pregnancy outcomes. Some of the biochemical placental markers - pregnancy associated plasma protein A (PAPP-A) and free-β human chorionic gonadotropin (hCG), probably could provide a diagnostic value for GDM. The aim of our study was to assess if PAPP-A and hCG values were different among pregnant women with and without GDM and respectively, to tested their place in the early GDM screening. We conducted a retrospective, case-control study by reviewing the clinical database records of 662 pregnant women. The analysis includes the data for a two-year period. The patients included in the observation were divided into two groups - GDM group (n = 412) and Euglycemic group (n = 250). Early screening for GDМ between 9-12 weeks' gestation was performed in 173 of the women in the interventional group due to: registered fasting plasma glucose (FPG) above 5.1 mmol/L, obesity, macrosomia in previous pregnancies or family history for diabetes mellitus. The remaining 239 women underwent universal screening at 24-28 weeks' gestation. Mean serum levels of PAPP-A, hCG, FPG, and body mass index (BMI) were measured between 10-13 gestational weeks. Serum levels of PAPP-A and hCG are presented as multiples of the normal median (MoM), adjusted by maternal baseline characteristics and demographics. In patients who developed GDM during pregnancy, compared with the control group, we have found significantly lower MoM values of PAPP-A (p < 0.0001), higher levels of FPG (р < 0.0001) and higher BMI (р < 0.0001). Median hCG MoM was similar in both group of pregnant women. Our findings suggest that low-normal to low reference range values of PAPP-A might be associated with higher risk for GDM. PAAP-A levels can be used as an additional factor to recommend early screening for GDM.

Analytical Comparison of Pregnancy-Associated Plasma Protein-A (PAPP-A) Immunoassays for Biochemical Determination of Gestational Age.

Accurate pregnancy dating is critical for maternal and child health and for counseling on safe and effective abortion methods. While last menstrual period and first trimester ultrasound are often used together to determine gestational age (GA), they have limited accuracy and availability, respectively. Prior studies have shown that pregnancy-associated plasma protein-A (PAPP-A) increases exponentially during pregnancy and has the potential to serve as a biochemical marker of GA. We aimed to analyze the relationship between sonographically determined GA and serum PAPP-A concentration measured by different immunoassays and to derive cutoff levels informative for the 70 days GA commonly recommended limit for medical abortion in outpatient settings. We compared technical characteristics of 4 commercially available PAPP-A immunoassays and tested 120 maternal serum samples (GA range: 34-231 days) along with contrived pool samples and traceable quality controls. These characteristics included area under the receiver operator characteristic (AUROC) plot, sensitivity and specificity based on cutoffs defined by the Youden Index, and likelihood ratios. All 4 immunoassays had sensitivities and specificities ≥80%, and AUROC values ranging from 0.948 to 0.968. Marked differences among absolute PAPP-A values were noted depending on immunoassay. PAPP-A cutoff values at 70 days GA for each individual immunoassay were established along with procedural recommendations that increase equivalence among immunoassays. Maternal serum PAPP-A levels correlated strongly with GA despite differences in immunoassay formats and absolute data output. Serum PAPP-A has biomarker potential for future development of a point-of-care test aimed at increasing access to medical abortion.

Correlation analysis of serum placental growth factor, pregnancy-related plasma protein-A and disease severity in patients with hypertensive disorder in pregnancy.

To analyze the correlation of serum placental growth factor (PLGF), pregnancy-associated plasma protein-A (PAPP-A) and disease severity in patients with hypertensive disorders in pregnancy (HDP). Altogether 88 pregnant women with hypertensive disorder who underwent prenatal examination and delivery in our hospital from March 2017 to February 2019 were selected and included as the research group (n=88), and 62 healthy pregnant women who underwent prenatal examination during the same period were included as the normal control group (n=62). Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of PAPP-A and PLGF in the serum of the two groups. The correlation of the expression levels of PAPP-A and PLGF with the severity of HDP was analyzed. The occurrence of adverse pregnancy outcomes in the two groups was compared, and the relationship of the expression levels of PAPP-A and PLGF with adverse pregnancy outcomes was compared. PAPP-A expression level in serum of pregnant women in the research group was significantly higher than that in the control group, while PLGF expression level was significantly lower than that in the control group (p<0.001). PAPP-A expression level was positively correlated with HDF severity (r=0.753, p<0.001), while PLGF expression level was negatively correlated with HDP severity (r=-0.929, p<0.001). The incidence of adverse pregnancy outcomes in the research group was significantly higher than that in the control group (p<0.05). The serum PAPP-A level of patients in the group with adverse pregnancy outcomes was significantly higher than that in the group without adverse pregnancy outcomes, while PLGF level was significantly lower than that in the group without adverse pregnancy outcomes (p<0.001). In conclusion, the expression levels of PAPP-A and PLGF in serum were closely related to the severity of HDP and could be used as indicators for disease monitoring.

Suppression of PAPP-A mitigates atherosclerosis by mediating macrophage polarization via STAT3 signaling

Pregnancy-associated plasma protein-A (PAPP-A), a type of metalloproteinase in the insulin-like growth factor (IGF) system, has been implicated in atherosclerosis progression, but its function and mechanism in atherosclerosis is not fully understood. The study was performed to further explore the effects of PAPP-A on inflammation, macrophage polarization and atherosclerosis. In mouse macrophages stimulated by oxidized low-density lipoprotein (ox-LDL), PAPP-A expression was significantly increased. Its knockdown markedly mitigated inflammatory response and polarized macrophages to an M2-like phenotype in RAW264.7 cells upon ox-LDL treatment. Additionally, ox-LDL-induced activation of nuclear factor-κB (NF-κB) signaling pathway was dramatically restricted by PAPP-A knockdown in macrophages. However, JAK2/STAT3 activation was significantly up-regulated in RAW264.7 cells with PAPP-A inhibition after ox-LDL treatment. Importantly, we found that PAPP-A knockdown-induced polarization of M2-like phenotype in macrophages was mainly dependent on STAT3 activation. Clinical studies showed that serum PAPP-A levels were higher in patients with coronary artery disease (CAD) than that of healthy individuals. Apolipoprotein E-knockout (ApoE−/-) mice with high fat diet (HFD)-induced atherosclerosis exhibited higher expression of PAPP-A in aortas, which was mainly colocalized with F4/80. Subsequently, we found that PAPP-A deficiency greatly alleviated plaque formation, lesion burden and collagen accumulation in HFD-fed ApoE−/- mice. Consistent with in vitro macrophage phenotype, PAPP-A−/− reduced F4/80 expression, NF-κB activation and inflammatory response, while improved janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling and polarized macrophages to an M2-like phenotype in aortas of ApoE−/- mice after HFD feeding. In conclusion, these findings identified PAPP-A as a positive regulator of atherosclerosis by regulating macrophage polarization via STAT3 signal, and thus could be considered as a potential therapeutic target for atherosclerosis treatment.